Lipotoxicity suppresses the synthesis of growth hormone in pituitary somatotrophs via endoplasmic reticulum stress.
J Cell Mol Med
; 25(11): 5250-5259, 2021 06.
Article
en En
| MEDLINE
| ID: mdl-33943005
ABSTRACT
Lipotoxicity has been shown to cause dysfunction of many organs and tissues. However, it is unclear whether lipotoxicity is harmful to the somatotrophs, a kind of cell that synthesize growth hormone (GH) in the pituitary. In this study, we performed an epidemiological study, serum levels of triglyceride (TG) and GH showed a negative correlation, even after adjustment for potential confounders. In an animal study, male Sprague-Dawley rats were fed a high-fat diet (HFD) or a control diet for 28 weeks. HFD rats showed impaired GH synthesis, resulting in a decrease in circulating GH levels. The expression of pituitary Pit-1, a key transcription factor of GH, was inhibited. We found that the inositol-requiring enzyme 1α (IRE1α) pathway of endoplasmic reticulum (ER) stress was triggered in HFD rat pituitary glands and palmitic acid-treated GH3 cells, respectively. On the contrary, applying 4-phenyl butyric acid (4-PBA) to alleviate ER stress or 4µ8c to specifically block the IRE1α pathway attenuated the impairment of both Pit-1 and GH expression. In conclusion, we demonstrated that lipotoxicity directly inhibits the synthesis of GH, probably by reducing Pit-1 expression. The IRE1α signaling pathway of ER stress may play an important role in this process.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Enfermedades de la Hipófisis
/
Hipófisis
/
Ácido Palmítico
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Hormona de Crecimiento Humana
/
Somatotrofos
/
Estrés del Retículo Endoplásmico
Tipo de estudio:
Observational_studies
/
Prevalence_studies
/
Risk_factors_studies
Límite:
Adult
/
Animals
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
J Cell Mol Med
Asunto de la revista:
BIOLOGIA MOLECULAR
Año:
2021
Tipo del documento:
Article
País de afiliación:
China